Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.49 (phosphoenolpyruvate carboxykinase)
 4,654 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In cultures of human and rat fetal liver, phosphoenolpyruvate carboxykinase activity increases during the first 24 hr of culturing. This increase can be suppressed by adding cycloheximide to the culture medium or by adding a high glucose concentration. This, however, applies only to human fetal liver and to fetal liver from rats obtained just before term. In younger rat fetal liver, glucose, on the contrary, increases the activity of phosphoenolpyruvate carboxykinase. A high glucose concentration in the medium also leads to higher citrate cleavage enzyme activity and to lower alpha-glycerolphosphate dehydrogenase (cytoplasmic) activity in rat fetal liver cultures.
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PMID:High glucose concentration and phosphoenolpyruvate carboxykinase activity in human and rat fetal liver cultures. 123 92

In parenchymal cells from starved mice L-tryptophan is a potent inhibitor of gluconeogenesis from substrates giving rise to oxaloacetate. Quinolinate yields a different pattern of inhibition and is generally much less effective. Tryptamine, indole 3-acetaldehyde and indole 3-acetate are equally as effective as tryptophan. Tryptamine inhibition alone may be overcome by pargyline; serotonin does not prevent the inhibition due to tryptophan. In kidney slices from starved rats, however, tryptophan has no effect on gluconeogenesis. Indole 3-acetate is also relatively ineffective, but quinolinate is signficiantly more potent than in liver; at 0.1mM, glucose production from lactate is 50% inhibited. Quinolinate is less effective with citric acid cycle substrates; the pattern of inhibition is consistent with a direct action on phosphoenolpyruvate carboxykinase. There is no evidence that glutamate dehydrogenase is simultaneously inhibited.
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PMID:Effect of tryptophan and its metabolites on gluconeogenesis in mammalian tissues. 124 97

The 3-day-old rat has a high basal level of phosphoenolpyruvate carboxykinase (PEPCK), the activity of which is not increased upon starvation. The lower basal activity of the enzyme in 19-day-old rat liver can, however, be stimulated by starvation. Serum glucose levels increased from 3 days to 19 days of age, with a decrease to adult levels. Liver glycogen concentration increased from 3 days to 19 days of age, with no additional increase observed at 3 months. There was a decrease with age in the specific activity of liver glycogen (from [14C]alanine and [14C]leucine). In fed rats given [14C]alanine, 14CO2 expiration tended to decrease with age. The 14CO2 production from [14C]leucine was less than that from alanine, and also decreased with age. Three-day-old rats showed no change in serum glucose when starved for 4 hr. On the other hand, 19-day-old rats responded with a decrease in serum glucose; although the adult animal's basal level of serum glucose was less than that of the 19-day-old rats, starvation for 15 hr also caused a significant decrease. There was no statistically significant difference in liver glycogen concentration between the fed and starved 3-day-old animals. Liver glycogen concentration in the 19-day-old adult rats was affected, however, by starvation. The 3-day-or glycogen during starvation. Starvation resulted in a tremendous increase in the specific activity of hepatic glycogen in the 19-day-old and adult rats. Starvation decreased the percentage of labeled amino acid expired as 14CO2. The proportion expired also decreased with age. Urinary nitrogen concentration increased significantly between 3 and 19 days of age. Starvation produced differential effects in the animals, with no change being observed in either the 3-day or adult rats; a decrease was observed in the 19-day-old animals. Urinary nitrogen concentration was measured in adult carbohydrate-deprived rats and was significantly higher than control values. These rats had a high gluconeogenic rate, reflected in the increased urinary nitrogen concentration. The young rat is at the mercy of a continuous supply of substrate in that it has a limited capacity for directing substrat
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PMID:Utilization of dietary amino acids for energy production in neonatal rat liver. 125 Jun 45

In vitro rates of lactate conversion to glucose and oxidation to CO2 were determined in livers of stress-susceptible (SS) and stress-resistant (SR) pigs because we hypothesized that livers of SS pigs had a lower capacity than livers of SR pigs to remove lactate from blood. Stress-susceptibility was determined by reaction to halothane at 7 weeks of age. At approximately 9 weeks of age, pigs were assigned to one of three experimental diets. Pigs weighing 95 kg were slaughtered immediately after stress, and liver samples were obtained. Incorporation of lactate into glucose in liver of SS pigs was 38% of that in SR pigs. Addition of either vitamin C or vitamins C and E plus magnesium oxide and collagen extract to a corn-soy diet did not alter lactate conversion to glucose, but depressed lactate oxidation to CO2. No differences were detected in either activities of lactate dehydrogenase, HAD-malate dehydrogenase, phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase, and glucose-6-phosphatase or concentration of glycogen in livers of SS and SR pigs. Our data indicate that livers of SS pigs possess a lower capacity to incorporate lactate into glucose and to oxidize lactate to CO2; maximal activities of enzymes measured in this study are not the cause of these differences. Reduced capacity of lactate metabolism in livers of SS pigs seems a part of the etiology of the porcine stress syndrome.
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PMID:Gluconeogenesis from lactate in liver of stress-susceptible and stress-resistant pigs. 126 79

Gluconeogenesis was studied in 3 cases of persistent neonatal hypoglycaemia. In 2 of the cases the labelling of blood glucose after i.v. injection of 1415C-alanine was reduced. In these 2 patients only 1.3-5% of the injected radioactivity was recovered in blood glucose, compared with 10% in normoglycaemic patients. The labelling of glucose from 14C-glycerol, as studied in one case, was not reduced. In this patient the labelling of blood glucose from C-alanine was improved after subtotal resection of the pancreas, and with increasing age. By the time of the isotope studies the plasma insulin was normal in all patients, and no deficiency of glucagon secretion could be detected after stimulation with an alanine load. A quantitative amino acid analysis of plasma revealed a moderate increase of some of the glucogenic amino acids. The results were interpreted as a deficiency of gluconeogenesis, probably at the phosphoenolpyruvate carboxykinase or pyruvate carboxylase step.
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PMID:Gluconeogenesis in infancy and childhood. II. Studies on the glucose production from alanine in three cases of persistent neonatal hypoglycaemia. 127 63

The effect of human recombinant tumor necrosis factor (TNF)-alpha on enzymes of gluconeogenesis in the rat was investigated by determining the activity of glucose 6-phosphatase, fructose 1,6-diphosphatase (FDP), and phosphoenolpyruvate carboxykinase in the liver and kidney of fed and fasted rats. The activity of transaldolase in the pentose phosphate pathway was also measured. Starvation of rats for 24 hr resulted in a 1.6- to 3.1-fold increase in liver and kidney glucose 6-phosphatase and phosphoenolpyruvate carboxykinase (P less than or equal to 0.05), a decrease in liver and kidney FDP (P less than 0.002), and an increase in liver and kidney transaldolase (P = 0.0001). Injection of 50 and 100 micrograms/kg/day of TNF for 5 days resulted in a significant (P less than or equal to 0.03) decrease in kidney FDP only. Injection of 100 micrograms/kg/day of TNF for 5 days with a 24-hr fast on Day 5 resulted in a significant (P = 0.04) increase in liver transaldolase, and a significant decrease in kidney FDP and phosphoenolpyruvate carboxykinase. Comparison of the enzyme activities of rats injected with 100 micrograms/kg/day of TNF for 5 days with those of their pair-fed control partners revealed additionally a significant decrease in glucose 6-phosphatase in the liver (P less than 0.001). It is concluded that TNF administration in the rat has different effects on the enzymes of gluconeogenesis in the liver and kidney, and these effects differ from those seen in starved or tumor-bearing rats.
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PMID:Effect of tumor necrosis factor on enzymes of gluconeogenesis in the rat. 130 99

Twenty-four male (12 obese and 12 lean) and 21 female (11 obese and 10 lean) SHR/N-cp rats were fed a diet containing either 54% sucrose or starch for periods of 3-4 months. Rats were killed after a 14-16 h fast and liver enzyme activities were determined in both sex groups. Liver glucose-6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), malic enzyme (ME), phosphofructokinase (PFK), glucokinase (GK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (per total liver capacity) were significantly affected by phenotype (obese > lean). Arginase and ornithine transcarbamylase levels were analysed only in male rats and were found to be elevated in obese rats as compared to lean littermates. Some of the above changes in enzyme levels were exaggerated by sucrose feeding but not the changes in FBPase, PEPCK, ME and GK (in both sexes) plus AST, arginase and arginine synthase activities in male rats and ALT levels in female rats. Results from SHR/N-cp rats published in this paper were compared to results obtained from LA/N-cp rats published previously. Comparison of the non-diabetic obese LA/N-cp with the diabetic obese SHR/N-cp male shows a greater excess in lipogenic capacity of the liver in the LA/N-cp male rat. The SHR/N-cp obese female also shows a greater liver lipogenic capacity as compared with the obese male SHR/N-cp rat. The results suggest that an adaptation of excessive lipogenesis in the liver of obese rats may be an anti-diabetogenic adaptation resulting in increased glucose conversion to lipids, thus reducing blood glucose levels.
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PMID:Adaptation in enzyme (metabolic) pathways to obesity, carbohydrate diet and to the occurrence of NIDDM in male and female SHR/N-cp rats. 133 Sep 56

Short- and long-term regulation of hepatic carbohydrate metabolism by insulin-like growth factor II was studied in primary cultures of adult rat hepatocytes and compared to the metabolic potency of insulin. Insulin-like growth factor II stimulated glycogen synthesis from [14C]glucose, uptake of [3H]aminoisobutyric acid and [14C]lactate formation from [14C]glucose up to three-fold. Basal glycogenolysis was inhibited to about 10%, and glucagon-activated glycogenolysis was blocked completely. The enzymatic activity of glucokinase and pyruvate kinase was induced two-fold, the glucagon-dependent induction of phosphoenolpyruvate carboxykinase was antagonized. Compared to insulin, half-maximal responses required up to 50 times higher insulin-like growth factor II concentrations ranging from 10-20 nmol/l. A similar difference was observed for binding affinity of insulin-like growth factor II to the insulin receptor. The interaction with the insulin-like growth factor II/mannose 6-phosphate (IGF-II/Man-6-P) receptor was examined by studying 125I-insulin-like growth factor II binding and uptake of lysosomal enzymes. The affinity of insulin-like growth factor II to the IGF-II/Man-6-P receptor was considerably higher than for the insulin receptor. Antibodies against the IGF-II/Man-6-P receptor did not affect metabolic responses to insulin-like growth factor II, while binding to its receptor and the receptor-mediated endocytosis of arylsulphatase A were strongly inhibited. Thus, in adult rat liver insulin-like growth factor II appeared to exert metabolic actions not via interaction with its own receptor but through low affinity binding to hepatic insulin receptors.
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PMID:Metabolic actions of insulin-like growth factor II in cultured adult rat hepatocytes are not mediated through the insulin-like growth factor II receptor. 134 10

Incubation of isolated hepatocytes from fasted rats with 20 mM LiCl for 1 h decreased glucose production from lactate, pyruvate, and alanine. In addition, phosphoenolpyruvate carboxykinase (PEPCK) gene expression in FTO-2B rat hepatoma cells was inhibited by treatment with LiCl. Lithium was also able to counteract the increased PEPCK mRNA levels caused by both Bt2cAMP and dexamethasone, in a concentration-dependent manner. A chimeric gene containing the PEPCK promoter (-550 to +73) linked to the amino-3-glycosyl phosphotransferase (neo) structural gene was transduced into FTO-2B cells using a Moloney murine leukemia virus-based retrovirus. In these infected cells, 20 mM LiCl decreased both the concentration of neo mRNA transcribed from the PEPCK-neo chimeric gene and mRNA from the endogenous PEPCK gene. Lithium also inhibited the stimulatory effect of Bt2cAMP and dexamethasone on both genes. The stability of neo mRNA was not altered by lithium, since in cells infected with retrovirus containing only the neo gene transcribed via the retroviral 5'-LTR and treated with 20 mM LiCl, no change in neo mRNA levels was observed. The intraperitoneal administration of LiCl to rats caused a decrease in hepatic PEPCK mRNA, indicating that lithium could also modify gene expression in vivo. The effects of lithium were not due to an increase in the concentration of insulin in the blood but were correlated with an increase in hepatic glycogen and fructose 2,6-bisphosphate levels. These results indicate that lithium ions, at concentrations normally used therapeutically for depression in humans, can inhibit glucose synthesis in the liver by a mechanism which can selectively modify the expression of hepatic phosphoenolpyruvate carboxykinase.
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PMID:Lithium inhibits hepatic gluconeogenesis and phosphoenolpyruvate carboxykinase gene expression. 137 Nov 8

New hepatocyte-like cell lines (mhAT) were derived from the liver of a transgenic mouse expressing SV40 early genes under the direction of the liver-specific antithrombin III gene promoter (ATIII-TSV40). Their differentiated phenotypes were improved and stabilized by the use of liver-specific growth media (arginine-free, glucose-free, or low-fructose/glucose-free medium). The best differentiated lines display a very high level of albumin, transferrin, and L-type pyruvate kinase (L-PK) gene expression that is comparable to that observed in the mouse liver. Abundance of the aldolase B and phosphoenolpyruvate carboxykinase (PEPCK) transcripts varied from 5 to 35% of the in vivo concentrations while abundance of the alpha-fetoprotein and phenylalanine hydroxylase transcripts remained very low. Hormonal (cAMP and insulin) and nutritional (glucose) gene controls of PEPCK and L-PK were, at least partially, conserved. mhAT cells are readily transfectable by the calcium phosphate coprecipitation technique and exhibit a liver-specific pattern of expression of exogenous genes. Thus, mhAT cells seem suitable for the analysis of the regulatory regions involved in the tissue-specific transcription of genes. This work demonstrates, therefore, the great efficiency of targeted carcinogenesis in transgenic mice to create new differentiated cell lines. The availability of various lines of liver-specific cells with different phenotypes will constitute useful tools to establish correlations between expression of trans-acting factors and control of the phenotype.
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PMID:Gene expression in hepatocyte-like lines established by targeted carcinogenesis in transgenic mice. 137 87


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